tbuckley/cabot-search huggingface dataset:
ExplaiNN: interpretable and transparent neural networks for genomics
Authors: Gherman Novakovsky, Oriol Fornes, Manu Saraswat, Sara Mostafavi, Wyeth W. Wasserman
Journal: Genome biology (2023)

Deep learning models such as convolutional neural networks (CNNs) excel in genomic tasks but lack interpretability. We introduce ExplaiNN, which combines the expressiveness of CNNs with the interpretability of linear models. ExplaiNN can predict TF binding, chromatin accessibility, and de novo motifs, achieving performance comparable to state-of-the-art methods. Its predictions are transparent, providing global (cell state level) as well as local (individual sequence level) biological insights into the data. ExplaiNN can serve as a plug-and-play platform for pretrained models and annotated position weight matrices. ExplaiNN aims to accelerate the adoption of deep learning in genomic sequence analysis by domain experts.
Working Toward Greater Transparency to Improve the Management of Research Misconduct
Authors: Jacqueline S. Jeruss, Rebecca M. Cunningham
Journal: JAMA Network Open (2023)

Susan Garfinkel, PhD; Sabina Alam, PhD; Patricia Baskin, MS; Christina Bennett, PhD; Bridget Carruthers, PhD; Jeffrey Engler, PhD; Annette Flanagin, RN, MA; Sheila Garrity, JD, MPH, MBA; Chris Graf, BS; Michael J. Imperiale, PhD; Christopher King, DVM; Sabine Kleinert, MD; Dan Kulp, PhD; Courtney Mankowski, BS; Nicola Nugent, PhD; Teodoro Pulvirenti, PhD; Lauran Qualkenbush, BS; Emily Sobiecki, JD; Daniel Wainstock, PhD; Erica Wilfong, MSc; Loren Wold, PhD; Jennifer Yucel, PhD
Gauging the Success of Low-Voltage-Area Ablation
Authors: Kristen K. Patton
Journal: JAMA Cardiology (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
Tobacco exposure primes the secretion of CCL21 positively associated with tertiary lymphoid structure and response to immunotherapy
Authors: Xuewen Yin, Hui Wang, Rutao Li, Xuming Song, Te Zhang, Yingkuan Liang, Yu-Zhong Chen, Xinnian Yu, Qixing Mao, Wenjie Xia, Bing Chen, Lin Xu, Gaochao Dong, Feng Jiang
Journal: Journal for ImmunoTherapy of Cancer (2023)

Background It has been reported that smoking history as a predictor of immunotherapy efficacy in patients with advanced lung cancer, however, the underlying mechanisms of this phenomenon remain largely unknown. Methods The patients with lung adenocarcinoma’s (LUAD) cohort and the orthotopical transplanted mouse model were used to explore the correlation between smoking status and tertiary lymphoid structure (TLS) and chemokine CCL21, respectively. Cell adhesion and co-immunoprecipitation assays were performed to explore the interaction between CD4+T cells and CD20+B cells under tobacco exposure. Chromatin immunoprecipitation-PCR was used to dissect the mechanism of upregulated CCL21 secretion in tobacco treatment. Serum CCL21 level was recorded in patients with LUAD treated with immunotherapy. Results Here we observed that individuals with a smoking history exhibit an increased quantity and maturation level of TLS compared with non-smokers, along with higher levels of CCL21 secretion. Tobacco exposure promoted CCL21 expression in an epithelial cell-intrinsic manner, of which BaP, the main component of tobacco, facilitated the nuclear retention of the aryl hydrocarbon receptor that occupied the promoter of CCL21. Additionally, the activated CCL21/CCR7 axis increased the CD11a expression of CD4+T cells, boosting the interaction with CD20+B cells dependent on ICAM1, which potentially induced the TLSs formation. Patients with elevated serum levels of CCL21 benefited more from immunotherapy. Conclusions Patients with a smoking history exhibited higher levels of TLS via the CCL21-dependent mechanism, serum CCL21 was identified as a reliable biomarker for predicting the efficacy of immunotherapy.
A Sequential Adaptive Intervention Strategy Targeting Remission and Functional Recovery in Young People at Ultrahigh Risk of Psychosis
Authors: Patrick D. McGorry, Cristina Mei, G. Paul Amminger, Hok Pan Yuen, Melissa Kerr, Jessica Spark, Nicky Wallis, Andrea Polari, Shelley Baird, Kate Buccilli, Sarah-Jane A. Dempsey, Natalie Ferguson, Melanie Formica, Marija Krcmar, Amelia L. Quinn, Yohannes Mebrahtu, Arlan Ruslins, Rebekah Street, Cassandra Wannan, Lisa Dixon, Cameron Carter, Rachel Loewy, Tara A. Niendam, Martha Shumway, Barnaby Nelson
Journal: JAMA Psychiatry (2023)

Clinical trials have not established the optimal type, sequence, and duration of interventions for people at ultrahigh risk of psychosis.
Dual Inhibition of KRASG12D and Pan-ERBB Is Synergistic in Pancreatic Ductal Adenocarcinoma
Authors: Kevin Christian Montecillo Gulay, Xinlian Zhang, Vasiliki Pantazopoulou, Jay Patel, Edgar Esparza, Deepa Sheik Pran Babu, Satoshi Ogawa, Jonathan Weitz, Isabella Ng, Evangeline S. Mose, Minya Pu, Dannielle D. Engle, Andrew M. Lowy, Hervé Tiriac
Journal: Cancer Research (2023)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with a low survival rate. Recently, new drugs that target KRASG12D, a common mutation in PDAC, have been developed. We studied one of these compounds, MRTX1133, and found it was specific and effective at low nanomolar concentrations in patient-derived organoid models and cell lines harboring KRASG12D mutations. Treatment with MRTX1133 upregulated the expression and phosphorylation of EGFR and HER2, indicating that inhibition of ERBB signaling may potentiate MRTX1133 antitumor activity. Indeed, the irreversible pan-ERBB inhibitor, afatinib, potently synergized with MRTX1133 in vitro, and cancer cells with acquired resistance to MRTX1133 in vitro remained sensitive to this combination therapy. Finally, the combination of MRTX1133 and afatinib led to tumor regression and longer survival in orthotopic PDAC mouse models. These results suggest that dual inhibition of ERBB and KRAS signaling may be synergistic and circumvent the rapid development of acquired resistance in patients with KRAS mutant pancreatic cancer. Significance: KRAS-mutant pancreatic cancer models, including KRAS inhibitor–resistant models, show exquisite sensitivity to combined pan-ERBB and KRAS targeting, which provides the rationale for testing this drug combination in clinical trials.
PD-1 Monotherapy Reigns Supreme in Adjuvant Melanoma…But for How Long?
Authors: Ryan C. Augustin, Jason J. Luke
Journal: Clinical Cancer Research (2023)

The results of CheckMate-238 led to the original FDA approval of anti-PD-1 therapy in high-risk, resectable melanoma. In this CCR Translations, we discuss the 5-year update of this pivotal trial and contextualize its results in the face of limited survival data, neoadjuvant therapy, next-generation biomarkers, and novel immunotherapy combinations. See related article by Larkin et al., p. 3352.
No evidence of isotretinoin sensitization in peanut-allergic children: a cross-sectional study
Authors: Emma Ruth, Fionnuala Heraghty, Niamh Flynn, Triona McGlynn, Paul J Turner, Maeve Kelleher, Aideen Byrne, Jonathan O’B. Hourihane
Journal: British Journal of Dermatology (2023)

The European Medicines Agency (EMA) advises that all medicines containing soya-derived excipients should be labelled as contraindicated in peanut-allergic individuals. This is despite evidence of very little cross-reactivity between soya and peanut allergies. It is highly unlikely that patients with peanut allergy are at risk of a cross-reactive soya oil-based allergic reaction to soya protein in isotretinoin. This cross-sectional study has demonstrated the absence of IgE-sensitization to isotretinoin in peanut-allergic children and adolescents. Isotretinoin does not need to be avoided by peanut-allergic patients and we would encourage the EMA to alter their advice regarding soybean oil-containing medications to reflect this.
Equity in Cardio-Oncology Care and Research: A Scientific Statement From the American Heart Association
Authors: Daniel Addison, Mary Branch, Alan H. Baik, Michael G. Fradley, Tochi Okwuosa, Kerryn W. Reding, Kathleen E. Simpson, Giselle Alexandra Suero-Abreu, Eric H. Yang, Clyde W. Yancy
Journal: Circulation (2023)

Advances in cancer therapeutics have revolutionized survival outcomes in patients with cancer. However, cardiovascular toxicities associated with specific cancer therapeutics adversely affect the outcomes of patients with cancer. Recent studies have uncovered excess risks of these cardiotoxic events, especially in traditionally underrepresented populations. Despite advances in strategies to limit the risks of cardiovascular events among cancer survivors, relatively limited guidance is available to address the rapidly growing problem of disparate cardiotoxic risks among women and underrepresented patient populations. Previously decentralized and sporadic evaluations have led to a lack of consensus on the definitions, investigation, and potential optimal strategies to address disparate cardiotoxicity in contemporary cancer care (eg, with immunotherapy, biologic, or cytotoxic therapies) settings. This scientific statement aims to define the current state of evidence for disparate cardiotoxicity while proposing uniform and novel methodological approaches to inform the identification and mitigation of disparate cardio-oncology outcomes in future clinical trials, registries, and daily clinical care settings. We also propose an evidence-based integrated approach to identify and mitigate disparities in the routine clinical setting. This consensus scientific statement summarizes and clarifies available evidence while providing guidance on addressing inequities in the era of emerging anticancer therapies.
Clinical Activity of Combined Telomerase Vaccination and Pembrolizumab in Advanced Melanoma: Results from a Phase I Trial
Authors: Espen B. Ellingsen, Steven O'Day, Artur Mezheyeuski, Agnieszka Gromadka, Trevor Clancy, Timothy S. Kristedja, Mohammed Milhem, Yousef Zakharia
Journal: Clinical Cancer Research (2023)

Cancer vaccines represent a novel treatment modality with a complementary mode of action addressing a crucial bottleneck for checkpoint inhibitor (CPI) efficacy. CPIs are expected to release brakes in T-cell responses elicited by vaccination, leading to more robust immune responses. Increased antitumor T-cell responses may confer increased antitumor activity in patients with less immunogenic tumors, a subgroup expected to achieve reduced benefit from CPIs alone. In this trial, a telomerase-based vaccine was combined with pembrolizumab to assess the safety and clinical activity in patients with melanoma.Thirty treatment-naïve patients with advanced melanoma were enrolled. Patients received intradermal injections of UV1 with adjuvant GM-CSF at two dose levels, and pembrolizumab according to the label. Blood samples were assessed for vaccine-induced T-cell responses, and tumor tissues were collected for translational analyses. The primary endpoint was safety, with secondary objectives including progression-free survival (PFS), overall survival (OS), and objective response rate (ORR).The combination was considered safe and well-tolerated. Grade 3 adverse events were observed in 20% of patients, with no grade 4 or 5 adverse events reported. Vaccination-related adverse events were mostly mild injection site reactions. The median PFS was 18.9 months, and the 1- and 2-year OS rates were 86.7% and 73.3%, respectively. The ORR was 56.7%, with 33.3% achieving complete responses. Vaccine-induced immune responses were observed in evaluable patients, and inflammatory changes were detected in posttreatment biopsies.Encouraging safety and preliminary efficacy were observed. Randomized phase II trials are currently ongoing.
Universal chromatin state annotation of the mouse genome
Authors: Ha Vu, Jason Ernst
Journal: Genome biology (2023)

Abstract A large-scale application of the “stacked modeling” approach for chromatin state discovery previously provides a single “universal” chromatin state annotation of the human genome based jointly on data from many cell and tissue types. Here, we produce an analogous chromatin state annotation for mouse based on 901 datasets assaying 14 chromatin marks in 26 cell or tissue types. To characterize each chromatin state, we relate the states to external annotations and compare them to analogously defined human states. We expect the universal chromatin state annotation for mouse to be a useful resource for studying this key model organism’s genome.
Laying the Groundwork for Optimized Surgical Feedback
Authors: Eugene Shkolyar, Carla Pugh, Joseph C. Liao
Journal: JAMA Network Open (2023)

Elyssa Y. Wong, BS; Timothy N. Chu, BS; Runzhuo Ma, MD; Istabraq S. Dalieh, BS, MS; Cherine H. Yang, BA; Ashwin Ramaswamy, MD, MPP; Luis G. Medina, MD; Rafal Kocielnik, PhD; Seyedeh-Sanam Ladi-Seyedian, MD; Andrew Shtulman, PhD; Steven Y. Cen, PhD; Mitchell G. Goldenberg, MD, PhD; Andrew J. Hung, MD
Improvements in Physical Function and Pain Interference and Changes in Mental Health Among Patients Seeking Musculoskeletal Care
Authors: Wei Zhang, Som P. Singh, Amdiel Clement, Ryan P. Calfee, Janine D. Bijsterbosch, Abby L. Cheng
Journal: JAMA Network Open (2023)

Importance Among patients seeking care for musculoskeletal conditions, there is mixed evidence regarding whether traditional, structure-based care is associated with improvement in patients’ mental health. Objective To determine whether improvements in physical function and pain interference are associated with meaningful improvements in anxiety and depression symptoms among patients seeking musculoskeletal care. Design, Setting, and Participants This cohort study included adult patients treated by an orthopedic department of a tertiary care US academic medical center from June 22, 2015, to February 9, 2022. Eligible participants presented between 4 and 6 times during the study period for 1 or more musculoskeletal conditions and completed Patient-Reported Outcomes Measurement Information System (PROMIS) measures as standard care at each visit. Exposure PROMIS Physical Function and Pain Interference scores. Main Outcomes and Measures Linear mixed effects models were used to determine whether improvements in PROMIS Anxiety and PROMIS Depression scores were associated with improved PROMIS Physical Function or Pain Interference scores after controlling for age, gender, race, and PROMIS Depression (for the anxiety model) or PROMIS Anxiety (for the depression model). Clinically meaningful improvement was defined as 3.0 points or more for PROMIS Anxiety and 3.2 points or more for PROMIS Depression. Results Among 11 236 patients (mean [SD] age, 57 [16] years), 7218 (64.2%) were women; 120 (1.1%) were Asian, 1288 (11.5%) were Black, and 9706 (86.4%) were White. Improvements in physical function (β = −0.14; 95% CI, −0.15 to −0.13; P &amp;amp;lt; .001) and pain interference (β = 0.26; 95% CI, 0.25 to 0.26; P &amp;amp;lt; .001) were each associated with improved anxiety symptoms. To reach a clinically meaningful improvement in anxiety symptoms, an improvement of 21 PROMIS points or more (95% CI, 20-23 points) on Physical Function or 12 points or more (95% CI, 12-12 points) on Pain Interference would be required. Improvements in physical function (β = −0.05; 95% CI, −0.06 to −0.04; P &amp;amp;lt; .001) and pain interference (β = 0.04; 95% CI, 0.04 to 0.05; P &amp;amp;lt; .001) were not associated with meaningfully improved depression symptoms. Conclusions and Relevance In this cohort study, substantial improvements in physical function and pain interference were required for association with any clinically meaningful improvement in anxiety symptoms, and were not associated with any meaningful improvement in depression symptoms. Patients seeking musculoskeletal care clinicians providing treatment cannot assume that addressing physical health will result in improved symptoms of depression or potentially even sufficiently improved symptoms of anxiety.
Dual‐Responsive Turn‐On T<sub>1</sub> Imaging‐Guided Mild Photothermia for Precise Apoptotic Cancer Therapy
Authors: Sijie Song, Qi Wang, Jiangao Xie, Junduan Dai, Dilan Ouyang, Guoming Huang, Yuheng Guo, Chen Chen, Mengnan Wu, Tingjing Huang, Jingwen Ruan, Xiaofeng Cheng, Xucong Lin, Yu He, Elena A. Rozhkova, Zhaowei Chen, Huanghao Yang
Journal: Advanced Healthcare Materials (2023)

Apoptosis has gained increasing attention in cancer therapy as an intrinsic signaling pathway, which leads to minimal leakage of waste products from a dying cell to neighboring normal cells. Among various stimuli to trigger apoptosis, mild hyperthermia is attractive but confronts limitations of non-specific heating and acquired resistance from elevated expression of heat shock proteins. Here, a dual-stimulation activated turn-on T1 imaging-based nanoparticulate system (DAS) is developed for mild photothermia (≈43 °C)-mediated precise apoptotic cancer therapy. In the DAS, a superparamagnetic quencher (ferroferric oxide nanoparticles, Fe3 O4 NPs) and a paramagnetic enhancer (Gd-DOTA complexes) are connected via the N6-methyladenine (m6 A)-caged, Zn2+ -dependent DNAzyme molecular device. The substrate strand of the DNAzyme contains one segment of Gd-DOTA complex-labeled sequence and another one of HSP70 antisense oligonucleotide. When the DAS is taken up by cancer cells, overexpressed fat mass and obesity-associated protein (FTO) specifically demethylates the m6 A group, thereby activating DNAzymes to cleave the substrate strand and simultaneously releasing Gd-DOTA complex-labeled oligonucleotides. The restored T1 signal from the liberated Gd-DOTA complexes lights up the tumor to guide the location and time of deploying 808 nm laser irradiation. Afterward, locally generated mild photothermia works in concert with HSP70 antisense oligonucleotides to promote apoptosis of tumor cells. This highly integrated design provides an alternative strategy for mild hyperthermia-mediated precise apoptotic cancer therapy.
Self‐Aggregated Nanoscale Metal–Organic Framework for Targeted Pulmonary Decorporation of Uranium
Authors: Lei Chen, Xiaomei Wang, Mengping Chen, Qiwen Sun, Yemeng Chen, Xiaojie Zhang, Rui Hong, Yigong Xu, Jingwen Guan, Sheng Hong, Dehan Cao, Tingfeng Sun, Ximeng Li, Lanhua Chen, Juan Diwu
Journal: Advanced Healthcare Materials (2023)

The limited availability of effective agents for removing actinides from the lungs significantly restricts the effectiveness of medical treatments for nuclear emergencies. Inhalation is the primary route of internal contamination in 44.3% of actinide-related accidents, leading to the accumulation of radionuclides in the lungs and resulting in infections and potential tumor formation (tumorigenesis). This study focuses on the synthesis of a nanometal-organic framework (nMOF) material called ZIF-71-COOH, which is achieved by post-synthetic carboxyl functionalization of ZIF-71. The material demonstrates high and selective adsorption of uranyl, while also exhibiting increased particle size (≈2100 nm) when it aggregates in the blood, enabling passive targeting of the lungs through mechanical filtration. This unique property facilitates the rapid enrichment and selective recognition of uranyl, making nano ZIF-71-COOH highly effective in removing uranyl from the lungs. The findings of this study highlight the potential of self-aggregated nMOFs as a promising drug delivery system for targeted uranium decorporation in the lungs.
Weight Loss Does Not Improve Impaired Brain Responses in People With Obesity
Authors: Emily Harris
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Programming Cell‐Derived Vesicles with Enhanced Immunomodulatory Properties
Authors: Khaga R. Neupane, Geraldine S. Ramon, Brock Harvey, Byeong Chun, Surya P. Aryal, Abdullah A. Masud, J. Robert McCorkle, Jill M. Kolesar, Peter M. Kekenes‐Huskey, Christopher I. Richards
Journal: Advanced Healthcare Materials (2023)

Tumor-associated macrophages are the predominant immune cells present in the tumor microenvironment and mostly exhibit a pro-tumoral M2-like phenotype. However, macrophage biology is reversible allowing them to acquire an anti-tumoral M1-like phenotype in response to external stimuli. A potential therapeutic strategy for treating cancer may be achieved by modulating macrophages from an M2 to an M1-like phenotype with the tumor microenvironment. Here, programmed nanovesicles are generated as an immunomodulatory therapeutic platform with the capability to re-polarize M2 macrophages toward a proinflammatory phenotype. Programmed nanovesicles are engineered from cellular membranes to have specific immunomodulatory properties including the capability to bidirectionally modulate immune cell polarization. These programmed nanovesicles decorated with specific membrane-bound ligands can be targeted toward specific cell types including immune cells. Macrophage-derived vesicles are engineered to enhance immune cell reprogramming toward a proinflammatory phenotype.